Orbital- and millennial-scale Antarctic Circumpolar Current variability in Drake Passage over the past 140,000 years.

The Antarctic Circumpolar Current (ACC) plays a crucial role in global ocean circulation by fostering deep-water upwelling and formation of new water masses. On geological time-scales, ACC variations are poorly constrained beyond the last glacial. Here, we reconstruct changes in ACC strength in the central Drake Passage in vicinity of the modern Polar Front over a complete glacial-interglacial cycle (i.e., the past 140,000 years), based on sediment grain-size and geochemical characteristics. We found significant glacial-interglacial changes of ACC flow speed, with weakened current strength during glacials and a stronger circulation in interglacials. Superimposed on these orbital-scale changes are high-amplitude millennial-scale fluctuations, with ACC strength maxima correlating with diatom-based Antarctic winter sea-ice minima, particularly during full glacial conditions. We infer that the ACC is closely linked to Southern Hemisphere millennial-scale climate oscillations, amplified through Antarctic sea ice extent changes. These strong ACC variations modulated Pacific-Atlantic water exchange via the "cold water route" and potentially affected the Atlantic Meridional Overturning Circulation and marine carbon storage.

The late Holocene demise of a sublittoral oyster bed in the North Sea.

A fossil oyster bed (Ostrea edulis) was recently encountered offshore Helgoland (German Bight). Oysters are important filter feeders in marine environments and their habitat structure supports a large associated biodiversity. The European flat oyster Ostrea edulis has historically occurred in vast populations in the North Sea, but declined massively in the early 20th century. The ecological restoration of Ostrea habitats is a current focal point in the North Sea. To better understand the mechanisms that caused the local collapse of the oyster population, this study investigated the size structure, weight, and age of the shells, along with the spatial dimensions, seafloor properties, and environmental context of the oyster bed. The results show that the demise of the population occurred around 700 CE, ruling out excessive harvest as a driver of decline. Synchronicity of increased geomorphological activity of rivers and concurrent major land use changes in early medieval Europe suggest that increased sedimentation was a viable stressor that reduced the performance of the oysters. The shells provided no indication of a demographically poor state of the oyster bed prior to its demise, but manifested evidence of the wide-spread occurrence of the boring sponge Cliona sp. Our study challenges the assumption of a stable preindustrial state of the European flat oyster in the North Sea, and we conclude that the long-term variability of environmental conditions needs to be addressed to benchmark success criteria for the restoration of O. edulis.

Test deformation and chemistry of foraminifera as response to anthropogenic heavy metal input.

Benthic foraminifera are sensitive to environmental changes and widely used as tools to monitor pollution. Rising numbers of deformed tests are often used as indicator for elevated levels of heavy metals, but little is known about the relation between heavy metal incorporation into foraminiferal tests and the formation of test deformities. Here, two sediment cores from the south-eastern North Sea are compared, regarding the occurrence of deformed foraminiferal tests, foraminiferal test chemistry (ICP-MS) and bulk sediment Pb content (XRF). The total abundance of deformed foraminiferal tests seems not to align temporarily with historical heavy metal pollution. Therefore, we suggest that foraminifera react with test deformation to other environmental stressors than the studied heavy metals. Test chemistry reflects historical increased bulk sediment heavy metal content, despite a slight temporal offset. We propose that Pb (and Cd) are only incorporated into foraminiferal tests above a yet to be defined threshold of pollution.

[Effects of a Phone-Based Follow-Up Care After Inpatient Rehabilitation for Breast Cancer Patients - A Randomized Controlled Trial]. / Effekte der telefonischen Nachsorge in der onkologischen Rehabilitation nach Brustkrebs ­ Ergebnisse einer randomisierten Studie.

Background Benefit and long-term effects of rehabilitation and psychoeducational interventions after cancer therapy are still controversial discussed. Aim of the study was to evaluate feasibility and effects of a telephone-based follow-up intervention after oncological rehabilitation. Methods 172 breast cancer patients (age 27-54 years) were randomized after inpatient rehabilitation to a telephone-based intervention (phone calls every 4 weeks over 6 months) or control group. Patients were evaluated by standardized questionnaire (e. g. IRES-24, HADS, LZI, emotional thermometer, questionnaire "return to work") at T1 (start of rehabilitation), T2 (end of rehabilitation) and T3 (6 months after rehabilitation). Results 2-way-ANOVAs were performed to evaluate long-term effects. Main effects of IRES-24 and HADS were significant depending on time (IRES-24 F(2,116)=40.49, p<0.01 and HADS F(2,117)=31.50, p<0.01; (F(2,11 6)=31.19, p<0.01) but no significant differences between the intervention and control group were seen. Conclusions Telephone-based follow-up care is feasible with high patient acceptance. However an improvement of therapeutic effects in the intervention group were not be detected by IRES-24 and HADS questionnaire. Potential explanations may be the low "dosage" (duration/quantity of phone calls) of the intervention or the fact that in the last years multimodal treatment interventions were established in German rehabilitation centers leading to a so-called "ceiling effect" without significant effects of additional follow-up interventions.

[Chances and Potential of a Modern Surgical Skills Lab as Substantial Practical Part of the Study of Human Medicine - "The Magdeburg Model"]. / Chancen und Potenziale eines modernen chirurgisch geprägten SkillsLabs im Rahmen des Humanmedizinstudiums ­ das Magdeburger Modell.

Introduction: Surgical education of medical students within "skills labs" have not been standardised throughout Germany as yet; there is a substantial impact of available aspects such as personal and space at the various medical schools. Aim: The aim of this contribution is to illustrate the concept of a surgical skills lab in detail, including curricular teaching and integrated facultative courses at the Medical School, University of Magdeburg ("The Magdeburg Model") in the context of a new and reconstructed area for the skills lab at the Magdeburg's apprenticeship center for medical basic abilities (MAMBA). Method: We present an overview on the spectrum of curricular and facultative teaching activities within the surgical part of the skills lab. Student evaluation of this teaching concept is implemented using the programme "EvaSys" and evaluation forms adapted to the single courses. Results: By establishing MAMBA, the options for a practice-related surgical education have been substantially improved. Student evaluations of former courses presented within the skills lab and the chance of moving the skills lab into a more generous and reconstructed area led to a reorganisation of seminars and courses. New additional facultative courses held by student tutors have been introduced and have shown to be of great effect, in particular, because of their interdisciplinary character. Conclusion: Practice-related surgical education within a skills lab may have the potential to effectively prepare medical students for their professional life. In addition, it allows one to present and teach the most important basic skills in surgery, which need to be pursued by every student. An enthusiastic engagement of the Office for Student Affairs can be considered the crucial and indispensable link between clinical work and curricular as well as facultative teaching with regard to organisation and student evaluation. The practice-related teaching parts and contents at the surgical section of a skills lab should be integrated into the National Competence-based Catalogue of Teaching Aims in Medicine ("NKLM").

Glacial melting: an overlooked threat to Antarctic krill.

Strandings of marine animals are relatively common in marine systems. However, the underlying mechanisms are poorly understood. We observed mass strandings of krill in Antarctica that appeared to be linked to the presence of glacial meltwater. Climate-induced glacial meltwater leads to an increased occurrence of suspended particles in the sea, which is known to affect the physiology of aquatic organisms. Here, we study the effect of suspended inorganic particles on krill in relation to krill mortality events observed in Potter Cove, Antarctica, between 2003 and 2012. The experimental results showed that large quantities of lithogenic particles affected krill feeding, absorption capacity and performance after only 24 h of exposure. Negative effects were related to both the threshold concentrations and the size of the suspended particles. Analysis of the stomach contents of stranded krill showed large quantities of large particles ( > 10(6 )µm(3)), which were most likely mobilized by glacial meltwater. Ongoing climate-induced glacial melting may impact the coastal ecosystems of Antarctica that rely on krill.

Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems.

UNLABELLED: Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of systems biology. Two of the most critical steps in this approach are to construct dynamical models of biochemical reaction networks for large datasets and complex experimental conditions and to perform efficient and reliable parameter estimation for model fitting. We present a modeling environment for MATLAB that pioneers these challenges. The numerically expensive parts of the calculations such as the solving of the differential equations and of the associated sensitivity system are parallelized and automatically compiled into efficient C code. A variety of parameter estimation algorithms as well as frequentist and Bayesian methods for uncertainty analysis have been implemented and used on a range of applications that lead to publications. AVAILABILITY AND IMPLEMENTATION: The Data2Dynamics modeling environment is MATLAB based, open source and freely available at http://www.data2dynamics.org. CONTACT: andreas.raue@fdm.uni-freiburg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial.

PURPOSE: AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients. PATIENTS AND METHODS: Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation. RESULTS: Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed. CONCLUSION: Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.

[Acute scrotum in childhood]. / Akutes Skrotum im Kindesalter.

BACKGROUND: Due to the variety of differential diagnoses causing acute scrotum and their possible consequences, this finding is a challenge for diagnostic and therapeutic management in the daily clinical practice of paediatric medicine. PATIENTS AND METHODS: Through a defined time period, all consecutive paediatric patients of a tertiary surgical centre aged up to 16 years who were diagnosed with and treated for primary acute scrotum were prospectively registered and retrospectively evaluated for patient, finding and treatment (intervention) associated specifics in this systematic unicentric observational study (design: case series) to reflect daily clinical practice. RESULTS: A total of 141 cases with acute scrotum were enrolled in the study during the 10-year period from January 2000 to December 2009. Eight percent of cases (n = 11) showed bilateral findings. There were two age peaks: newborns and puberty. The most common diagnoses were epididymitis and orchitis (26 %), torsion of the testicular appendix (22 %) and testicular torsion (21 %). Trauma, hydrocele, inguinal hernia, idiopathic scrotal oedema and tumours were rather rare differential diagnoses as possible causes for an acute scrotum. The mean period of discomfort, complaints and symptoms up to presenting in the outpatient clinic was 24 hours. For sixty percent (n = 84, i.e., all patients treated conservatively and 43 % of the operated patients) an imaging study was obtained with ultrasound or Doppler ultrasonography, respectively. Two thirds of the patients underwent an operative exploration. The orchiectomy rate in testicular torsion amounted to 40 %. In one newborn, a bilateral orchiectomy was necessary. In patients with unilateral orchiectomy, a prophylactic fixation of the contralateral testis was performed preferentially at 4-8 weeks after the initial intervention even though a simultaneous procedure is being increasingly used. CONCLUSIONS: In approximately one fifth of registered patients, a testicular torsion is present causing the acute scrotum, and leading to an obligatory surgical intervention. Various causative differential diagnoses can be clarified by precise medical history and exact physical examination. Imaging procedures can be helpful in decision-finding. Finally, the clinical finding is crucial and decisive. If a testicular torsion cannot reliably be excluded by clinical investigation or imaging, an immediate surgical exploration of the testis has to be performed.

[Skills lab from the surgical point of view. Experiences from the Magdeburg Medical School--The University of Magdeburg]. / Skills Lab aus chirurgischer Sicht. Erfahrungen des Universitätsklinikums Magdeburg.

INTRODUCTION: For the acquisition of practical skills, the separate learning atmosphere of a skills lab(oratory) is very suitable. Numerous educational objectives of surgical teaching can be pursued using phantoms, manikins or mutual training among students prior to real practical use during clinical traineeships or internships. AIM AND METHOD: This article provides a compact, systematic overview of the skills lab concept, based on published aspects in selected and relatively recent topic-related references from PubMed® including our own approaches, as well as comments and experiences with regard to its further development. In particular, the Magdeburg concept to use the local skills lab MAMBA for surgical teaching within the practical training is demonstrated, which has developed step by step from a basically pure bedside teaching and which includes student tutors in practical teaching in surgery. RESULTS: By founding the Magdeburg educational and training center options for a practical education, in particular, in surgery were created. The great majority of students accepted the conceptual idea and it has so far been well received. As a first step several well selected topics of practical training during human medical studies were increasingly taught by students who received a didactic course of instruction which also included aspects of the educational objectives. For the future tutorials led by students are planned going beyond the teaching contents of the practical courses and can, thus, lead to a networking with educational objectives of other disciplines. There are not only curricular but also facultative courses in MAMBA which have been steadily optimized since the beginning. This Magdeburg's concept is planned to be further developed for which there is enough room for development with regard to organizational aspects (personnel and room).

[Therapeutic options for haemangiomas of infancy]. / Überblick der Therapiemöglichkeiten im Management von Säuglingshämangiomen.

The necessity of haemangioma treatment in infants has been controversially discussed for years. One reason is the favoured clinical observation of a potential spontaneous involution without any therapeutic approach or medical treatment, thus avoiding their specific risks. On the other hand, there are several reports on serious cases with -rapidly growing haemangiomas including severe consequences. There are potential complications such as loss of visus in cases of periorbital manifestation. A basic problem is the lack of a unique systematic classification, on the basis of which -diagnostic measures, therapeutic indications and modes could be compared. Such a classification would be much more competent including a sufficient comparison of treatment results. The basic aim in management is to achieve control of the haemangioma growth and induction of its sub-sequent involution back to only a cosmetic detraction. Each threatening functional loss can be classified as an urgent indication for treatment. There is a need to consider the treatment options and their values; in particular, cryotherapy or laser therapy in localised manifestations are mostly -favoured because of the convincing evidence from available data. In the case of a more disseminated haemangioma manifestation, the initiation of propranol medication is possible, a novel drug for this indication. However, there are no follow-up data on the mid-term or long-term outcome available at this time. Further studies on the subject are therefore required.

[Bilateral intrauterine testicular torsion in a newborn]. / Bilaterale intrauterine Hodentorsion bei einem Neugeborenen.

Bilateral intrauterine testicular torsion is a rare condition associated with a low salvage rate of the testes. Due to variable symptoms it is difficult to rapidly find the correct diagnosis. Here, we report on a newborn with bilateral livid swelling of the scrotum for which a bilateral orchiectomy was carried out. Histological investigation of the specimens confirmed bilateral hemorrhagic infarction. The management of bilateral intrauterine testicular torsion is still controversial. Immediate surgical intervention is still considered to be the treatment approach of choice to salvage the testes.

[What must the (abdominal) surgeon know about paediatric surgery - paediatric surgical aspects in general (abdominal) surgery]. / Was muss der (Viszeral-)Chirurg von der Kinderchirurgie wissen - kinderchirurgische Aspekte in der (Viszeral-)Chirurgie.

Due to the advances in neonatal intensive care medicine, prenatal ultrasound-guided diagnostic measures and paediatric surgical options, conditions have been established to achieve long-term survival in newborns with severe diseases. In addition, this means that the "non-paediatric" physician can be increasingly confronted with patients who would not have survived childhood some decades ago. Therefore, the article summarises concisely selected diseases of premature infants and newborns, e. g., congenital abdominal wall defects, and outlines possible long-term consequences based on the surgical interventions and their basic diseases, respectively, which need to be adequately cared for in the case of a surgical disease of the former patient of paediatric surgery. The overview cannot be considered as a complete revision course; however, it might constitute a basic outline for thought-provoking impulses for personal professional skills and expertise in managing such patients in later age from a surgical perspective.

Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.

BACKGROUND: The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy. METHODS: Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks). RESULTS: Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend. CONCLUSION: This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.

[Congenital abdominal wall defects--an analysis of prevalence and operative management by means of gastroschisis and omphalocele]. / Ventrale Bauchwanddefekte--Darstellung der Entwicklung in Prävalenz und operativem Vorgehen anhand von Gastroschisis und Omphalozele.

The management of congenital abdominal wall defects is one of the main characteristics of quality for a department of paediatric surgery. The results of treatment in the early years were the reason for a continuous improvement of procedures, operation strategies and the kinds of -material that had been used. During the last years there has been a great discussion about the presumed increase in the incidence of gastroschisis and the preterm delivery of such cases. On the basis of our own first results (2006-2009) and details from the literature, we survey these two topics.

[Incidental finding of an acute appendicitis in a premature newborn with haematochezia]. / Zufallsbefund einer akuten Appendizitis bei einem Frühgeborenen mit Hämatochezie.

In newborns, acute appendicitis is a very rare condition associated with significant lethality. Due to mostly non-specific symptoms, it is difficult to find the correct diagnosis preoperatively. Interestingly, rectal bleeding as a clinical sign in neonatal appendicitis is very uncommon. Here, we report on a 4-day-old premature female newborn with rectal bleeding who, therefore, underwent laparotomy because of a suspected volvulus. Except for an acutely inflamed appendix, no other pathological findings were found intraoperatively, leading to appendectomy. Histological investigation of the specimen confirmed acute ulcero-phlegmonous appendicitis. Thus, the rectal bleeding can be attributed to erosions as part of the inflammatory changes in clinically apparent appendicitis. The postoperative course of the patient was unremarkable, in perticular, no further rectal bleeding episode was observed. In spite of the low incidence of neonatal appendicitis, it has to be included in the spectrum of differential diagnoses if unclear abdominal discomfort occurs and whenever non-specific clinical signs are found in newborns. Early surgical intervention is considered the curative treatment approach of choice and can, thus, contribute to a reduction of the potential complications.

[Colon triplication associated with ileum atresia in laparoschisis]. / Kolon-Triplikatur assoziiert mit einer Ileum-Atresie bei Laparoschisis.

The present paper reports the unusual and rare case of a colon triplication associated with other findings never reported before, including the diagnostic and therapeutic management with consideration of the relevant, but rare scientific references in the medical literature. In the basic finding of an ileum atresia with laparoschisis, a colon triplication was incidentally found. The surgical procedure performed after the primarily planned Caesarean section within the 34(th) week of gravidity consisted of a bowel-preserving resection of the triplication including the ileum atresia and a subsequent Santulli anastomosis followed by a later excision of the ileostoma. Interestingly, this is the 9(th) reported case in the accessible English medical literature but, however, the first and only one with an associated ileum atresia and laparoschisis, which was successfully treated with a surgical intervention.